1. FDA/CBER - SOPP 8401: Administrative Processing of Biologics Licen... http://www.fda.gov/cber/regsopp/8401.htm
Manual of Standard Operating Procedures and
Policies
Regulatory - License Applications
Administrative Processing of Biologics License Applications (BLA)
SOPP 8401 Version #6 May 1, 2007
[Printable PDF of this document]
1. Purpose
This document provides policies and procedures to Center for Biologics Evaluation and Research (CBER)
staff on the administrative processing of the Biologics License Application (BLA).
2. Definitions
See the Appendix 1 for definitions and Appendix 2 for a list of abbreviations and acronyms used in this
SOPP.
3. Background
On October 20, 1999 the final rule "Biological Products Regulated Under Section 351 of the Public Health
Service Act; Implementation of the Biologics License; Elimination of the Establishment License and Product
License" was published (64 FR 56441). This final rule addressed procedures for handling of BLAs and
issuance of biologics licenses for all products subject to licensur e under the PHS Act, and it amended the
licensing regulations in 21 CFR 601 to reflect the changes to the licensing requirement of Section 351. The
final rule became effective December 20, 1999. Since then all new submissions have been handled as BLAs
using Form FDA 356h in lieu of filing an Establishment License Application (ELA) and Product License
Application (PLA).
4. Policy
All new marketing submissions for products subject to licensure under the PHS Act will be handled as BLAs
or supplements to BLAs. The procedures in this SOPP supplement additional CBER SOPPs (see references)
that describe administrative handling and review of license applications.
It is the policy of CBER that under normal circumstances product lot(s) should be available for distribution at
the time of approval of the BLA or supplement. Exceptions will be made on a case by case basis.
5. Roles, Responsibilities and Procedures
Office-specific SOPPs will address any additional responsibilities of the regulatory project manager (RPM),
1 of 12 8/8/2008 11:22 AM

2. FDA/CBER - SOPP 8401: Administrative Processing of Biologics Licen... http://www.fda.gov/cber/regsopp/8401.htm
reviewers, and Office staff. In no case will Office-specific SOPPs be applied across the board to review
committee members from other Offices.
The Division of Blood Applications (DBA), Office of Blood Research and Review (OBRR) will continue to
have full administrative responsibility for BLA issues related to licensed manufacturers of blood and blood
components.
I. Pre-BLA Activities
Requests for end-of phase 2, and/or pre-phase 3 and pre-BLA meetings will be processed
as amendments to the appropriate Investigational New Drug Application (IND). If no IND
exists, these requests and the associated meeting summaries will be entered in the CBER
Regulatory Meeting Tracking System (CRMTS) and the Pre-Application Tracking System
(PTS). Offices will follow the procedures outlined in SOPP 8114: Administrative
Processing of Documents Received Prior to Submitting Investigational or Marketing
Applications (Pre-Application).
If the subject of the pre-BLA meeting is to address facility or Division of Manufacturing
and Product Quality (DMPQ), Office of Compliance and Biologics Quality (OCBQ),
issues only, DMPQ will process the request for the meeting.
If the pre-BLA meeting request is for blood establishments, the Blood and Plasma Branch
(BPB), Division of Blood Applications (DBA), Office of Blood Research and Review
(OBRR) will process the request for the meeting.
The Regulatory Project Manager (RPM) assigned to the IND or submission will be the
primary contact for information on submission of the BLA and will coordinate the
following pre-BLA activities.
1. Schedules meetings in accordance with SOPP 8101.1: Scheduling and Conduct of
Regulatory Review Meetings with Sponsors and Applicants
a. Ensures appropriate participation in the meeting by representatives of all
review disciplines that will be involved in the review, starting with the
pre-BLA and continuing through the BLA. Participants should include:
1. Product and Clinical reviewers,
2. DMPQ/OCBQ,
3. Epidemiology and biostatistics reviewers in the Division of Biostatistics
(DB),Office of Biostatistics and Epidemiology (OBE)
4. Bioresearch Monitoring Branch (BiMo)/Division of Inspections and
Surveillance (DIS)/OCBQ,
5. Advertising and Promotional Labeling Branch (APLB)/Division of Case
Management (DCM), OCBQ
6. Electronic Submissions Coordinator (ESC) and
7. Consult reviewer from other Offices or Centers within the Agency as
appropriate.
b. Ensures meeting minutes are prepared
c. Completes a record of the meeting in CRMTS
d. Distributes meeting summary to FDA participants and requestor
2. For paper BLA submissions:
a. Coordinates with the applicant for the correct number of copies of pertinent
volumes of the BLA for all members of the review committee and consult
reviewers.
b. Notifies CBER's Document Control Center (DCC) of the expected arrival date
and size of the application.
c. Contacts DCC to make delivery arrangements for large submissions and
supplies DCC with sponsor/applicant contact information. DCC considers a
large submission to be one that exceeds a total of 50 volumes (including
copies) or about 5 cubic feet.
Office Electronic Submissions Coordinator (ESC)
2 of 12 8/8/2008 11:22 AM

3. FDA/CBER - SOPP 8401: Administrative Processing of Biologics Licen... http://www.fda.gov/cber/regsopp/8401.htm
1. Works with the applicant prior to submission (usually at the pre-BLA meeting) to
ensure appropriate procedures and formats for electronic submissions are followed.
2. Coordinates with the pertinent electronic submission coordinators (ESCs) in DMPQ,
DB, DCC, Office of Information Technology (OIT) and the Center electronic
submission coordinator (CESC). All ESCs should be notified as early as possible of
a potential electronic filing to ensure their readiness to process it efficiently.
3. Additional information on electronic submissions may be found at
http://www.fda.gov/cber/esub/esub.htm
II. BLA Activities: Receipt and Processing
Form FDA 356h should be submitted with all correspondence to CBER. This information will aid in
routing the submission to the appropriate division for processing.
A. Document Control Center (DCC): Receipt and Processing
1. Receives, logs in, and routes to the appropriate Office all BLAs and extra reviewer copies.
DCC will route the submission based on the product name as reported by the applicant on
the Form FDA 356h.
2. Electronic submissions will be processed per established procedures and the appropriate
ESCs notified (See DCC Procedure Guide 22: Procedures for Processing, Routing, and
Storing Electronic Submissions).
3. The original copy of the submission (paper and/or electronic) will be maintained in DCC
as an uncirculated record copy.
B. Regulatory Project Manager (RPM): Receipt and Processing
Upon receipt of the BLA in the product Office, the RPM will perform the following where
applicable:
1. Screens the BLA to confirm all the sections are present and consistent with the TOC.
Notifies the applicant of inconsistencies.
a. Determines the User Fee status and sends a copy of the user fee cover sheet, FDA
Form 3397 (PDUFA) or FDA Form 3601 (MDUFMA) to the Regulatory
Information Management Staff (RIMS) per SOPP 8406: Verification of User Fee
Data Sheet and Payment
b. Determines that an Environmental Assessment (EA) or request for Categorical
Exclusion (CE) has been submitted. 21 CFR 24.20-25.31 requires submission for
certain products. If an EA or CE was not submitted but may be needed, the RPM
will consult with DMPQ.
2. Ensures all required data is entered into the Regulatory Management System – Biologics
License Application (RMS-BLA) per the RMS-BLA User Guide
a. All reviewers, including those in DMPQ, OBE, APLB and BiMo should be listed as
committee members in RMS-BLA
3. Ensures that a Submission Tracking Number (STN) is assigned and that the STN
assignment letter is issued
4. Notifies all identified committee members and their supervisors in all Offices of the receipt
of the BLA
5. Ensures the submission is routed to all members of the review committee and all consult
reviewers
a. Requests additional copies from the applicant as needed
b. The DMPQ or BPB/DBA Reviewer will always receive a copy of the Chemistry,
Manufacturing, and Controls (CMC) and Establishment Description sections
c. A copy of the Table of Contents (TOC) should be sent to all committee members
d. Consults with APLB on all patient package inserts, prescribing information,
proposed proprietary names, logos, press releases, kits, and carton and container
labeling per SOPP 8001.4: Review of CBER Regulated Product Proprietary Names
and SOPP 8412: Review of Product Labeling.
1. (1) Note: Advertisements and promotional materials submitted per 21 CFR
3 of 12 8/8/2008 11:22 AM

4. FDA/CBER - SOPP 8401: Administrative Processing of Biologics Licen... http://www.fda.gov/cber/regsopp/8401.htm
314.550 and 601.45 for accelerated approval and restricted distribution
requirements should be routed to APLB/OCBQ. Including other draft
promotional materials submitted voluntarily for advisory comment by the
applicant.
6. Ensures a check is made with the PTS and cross-references are listed in the regulatory
databases. If appropriate, the PTS number is closed and the applicant notified.
III. BLA Activities: Filing Decision
A. Review Committee: Filing Decision
1. In consultation with the BiMo representative, determines what inspection (of clinical
investigators or sponsors) are necessary and appropriate
2. Each reviewer will evaluate the pertinent information in RMS-BLA for accuracy and
completeness upon receipt. If there are any additions/corrections needed, the review
committee member is responsible for notifying the RPM of the changes needed.
3. Each reviewer recommends the filing status to the committee chair.
4. Identifies any substantive deficiencies for communicating in the filing letter or the day 74
letter
5. Ensures all appropriate documentation is entered in RMS-BLA and either imported into
the Electronic Document Room (EDR) or forwarded to the RPM in a timely manner.
B. DMPQ or BPB lead: Filing Activities
1. Determines if a pre-approval establishment inspection is required (SOPP 8410:
Determining when Pre-License /Pre-Approval Inspections are Necessary)
C. Review Committee Chair: Filing Activities
1. Reviews the TOC and submission to make sure all applicable scientific disciplines have
been requested and relevant sections of the BLA are clearly assigned for review by the
committee members.(SOPP 8401.4: Review Responsibilities for the CMC Section of
Biologic License Applications and Supplements).
2. Determines the filing status of the submission considering all review members
recommendations.
a. Refusal to file a BLA may be based on deficiencies found in any section of the
submission per SOPP 8404: Refusal to File Guidance for Biologics License
Applications and 21 CFR 601.12.
3. Determines if an Advisory Committee meeting is necessary.
D. RPM: Filing Activities
1. Ensures changes are made if additions and/or corrections are necessary to RMS-BLA after
the review committee verifies the information.
2. Ensures that the filing decision is documented and a letter is sent to the applicant
NOTE: When a decision is made to file an application, the applicant must be notified in the
filing letter within 60 days of the receipt date. Potential issues may be identified in a
separate "deficiencies identified" or "no deficiencies identified" letter independent of the
filing letter within 14 days of the 60 day filing date. The 60 day filing date applies to either
potential review issues or no potential review issues identified during the filing review.
Refer to SOPP 8401.3 Filing Action: Communication Options, for communication
procedures.
E. Electronic Integrity Reviewer: Filing Activities
1. Upon notification of the load, checks the submission for "readability," (i.e., structure,
format, presence of bookmarks, hyperlink functionality, etc.) throughout the entire
submission.
2. If there is a problem with the submission, the ESC, in coordination with the CESC, will
contact the applicant, usually by teleconference. The RPM will usually be included in the
teleconference.
3. Troubleshoots with reviewers if there is difficulty accessing files, navigation, etc
IV. BLA: Review Activities
4 of 12 8/8/2008 11:22 AM

5. FDA/CBER - SOPP 8401: Administrative Processing of Biologics Licen... http://www.fda.gov/cber/regsopp/8401.htm
All actions with the exception of RMS-BLA data entry and review should be accompanied by written
documentation describing the decision reached, with justification as appropriate, and submitted to the
license application file by each member of the review committee.
A. Review Committee: Review Activities
1. Each member will be invited to attend all meetings and is expected to attend all appropriate
meetings
2. Conducts a comprehensive review of the submission including:
a. Identifying any issues including informational requests
b. Identifying issues that could prevent approval
c. Developing a clear plan for addressing issues including the decision to send a
Discipline Review (DR), Information Request (IR), or Complete Response (CR)
letter to the applicant
d. Provides letter ready comments/questions to the RPM
e. Makes any recommendations for review to go to an advisory committee
3. Reviews and concurs with all action letters for the application
4. Ensures that all appropriate documentation (review memos, telecons, etc) is entered in
RMS-BLA and either imported into the EDR or forwarded to the RPM in a timely manner
5. Identifies any issues related to promotional labeling
6. Consults with APLB on all patient package inserts, prescribing information, proposed
proprietary names, logos, press releases, kits, and carton and container labeling.
7. Identifies labeling content issues related to Physician's Labeling Rule (PLR) and data
element coding for Structured Product Labeling (SPL).
B. Discipline reviewer: Review Activities
1. Forwards final discipline review to supervisor(s) for concurrence.
C. CMC Reviewer/Product Lead: Review Activities
1. Enters information on animal materials in the Animal Component Database (ACD) per
SOPP 8401.5: Processing of Animal Component Information Submitted in Investigational
and Marketing Applications/Notifications.
2. Determines if testing of exhibit lots submitted in support of the BLA is necessary and in
collaboration with PRB, will determine the number of samples required. Communicates
these requirements to the committee chair.
3. Ensures that lot release protocols and exhibit product samples have been requested for lots
in support of the application per SOPP 8408: Collaboration of CBER Offices on Issues
Related to the Release of Pre-Licensing and Routing Lots
4. Drafts a CBER Lot Release Testing Plan for committee review and Office approval by the
mid-cycle review per SOPP 8408: Collaboration of CBER Offices on Issues Related to the
Release of Pre-Licensing and Routine Lots.
D. DMPQ reviewer: Review Activities
1. Reviews the Environmental Assessment (EA).
2. Prepares and signs the Finding of No Significant Impact (FONSI) when such a finding is
appropriate.
a. The FONSI is sent through and signed by the DMPQ Division director and the
Product Division Directors. The FONSI is forwarded to the RPM for inclusion in the
final action package.
3. Prepares a review memo for the categorical exclusion (CE) that takes the place of the
FONSI.
a. The applicant must apply for and be granted a categorical exclusion from the EA.
The CE memo is forwarded to the RPM for inclusion in the final action package.
E. BiMo reviewer: Review Activities
1. Issues BiMo inspection assignments consistent with the review milestones and the needs
identified by the review committee
2. Reviews BiMo inspection reports, identifies any issues related to data integrity, human
subject protection or other good clinical practice issues and follows up appropriately.
5 of 12 8/8/2008 11:22 AM

6. FDA/CBER - SOPP 8401: Administrative Processing of Biologics Licen... http://www.fda.gov/cber/regsopp/8401.htm
Communicates any issues which may have an impact on the submission to the review
committee.
3. Prepares appropriate correspondence for inspected parties. With concurrence from the
Bioresearch Monitoring Branch (BMB) Chief and DIS Director, issues correspondence.
4. Provides RPM with discipline review memo which summarizes the inspection results and
makes a formal recommendation regarding any substantive impact on the submission under
review.
5. Files domestic inspection reports and related correspondence under the IND inspection tab.
For foreign inspection, CBER retains the original inspection report and exhibits, issues the
inspected party the information copy of the inspection report according to the Field
Management Directive (FMD) 145, and files these reports in the IND if there is one, or in
the BLA if there is no corresponding IND.
F. APLB Reviewer: Review Activities
1. Prepares consult review memo for patient package insert, prescribing information,
proposed proprietary names, logos, press releases, kits, and carton and container labeling
for the RPM and committee chair.
2. Consult for product office on other "patient-friendly" materials, including detailed
"Instructions for Use" documents
3. Consult for product office on risk management programs, including MedGuides, Informed
Consent Documents, and patient education materials.
G. Product Release Branch (PRB): Review Activities
1. Notifies committee chair and CMC Reviewer(s)/Product Lead when exhibit samples and
protocols have been received per SOPP 8408: Collaboration of CBER Offices on Issues
Related to the Release of Pre-Licensing and Routine Lots.
2. Ensures that lot release protocols are under review and that testing is being performed.
3. Notifies the chair and CMC Reviewer(s)/Product Lead of any valid test failures of exhibit
lots.
H. Review Committee Chair: Review Activities
1. Ensures a mid-cycle review meeting is scheduled
2. Ensures advisory committee preparation is completed
3. Collaborates with PRB early in the review process (post filing) with regard to the CMC
reviewer's(s) draft Lot Release Testing Plan and recommendations on sample and test
protocol submission requirements as well as identification of individuals to conduct such
testing and review (see SOPP 8408: Collaboration of CBER Offices on Issues Related to
the Release of Pre-Licensing and Routine Lots).
I. RPM: Review Activities
1. Ensures compliance status check is initiated no less than 30 days prior to approval by
DVRPA, DBA, RMS, or DMPQ, when necessary, The compliance status check request is
entered in RMS-BLA by the requestor.
2. Notifies the Quality Assurance Staff (QAS) and Product Release Branch
(PRB)/DMPQ/OCBQ of the draft CBER Lot Release Testing Plan.
3. Schedules a mid cycle review meeting.
4. Ensures that lot release protocols and product samples have been submitted and are under
review and that testing is being performed.
5. Confirms that, when required, BiMo assignments have been issued.
J. Electronic Integrity Reviewer: Review Activities
1. Ensures that all amendments submitted conform for "readability," (i.e., structure, format,
presence of bookmarks, hyperlink functionality, etc.).
2. If there is a problem with the submission, the ESC, in coordination with the CESC, will
contact the applicant, usually by teleconference. The RPM will usually be included in the
teleconference.
3. Aid reviewers in accessing amendments.
V. BLA Activities: Communications
A. Review Committee: Communications
6 of 12 8/8/2008 11:22 AM

7. FDA/CBER - SOPP 8401: Administrative Processing of Biologics Licen... http://www.fda.gov/cber/regsopp/8401.htm
1. Review and concur on all action letters routed.
B. DBA/BPB Lead: Communications
1. Prepares letters for issues associated with blood and blood components only
a. Obtains concurrence from the BPB Branch Chief before the DBA Division Director
signs.
C. DMPQ Lead: Communications
1. Prepares letters if the only issues are establishment related and a product office is
administratively processing the BLA.
a. Requires concurrence from the DMPQ branch chief and division director and
appropriate individuals in the product office before the Office Director (or
designate) with product responsibility signs.
D. RPM: Communications
1. Coordinates the issuance of all letters including acknowledgement of major amendment,
Information Request (IR), Discipline Review (DR), Complete Response (CR) and
Approval letters in accordance with SOPP 8405: Complete Review and Issuance of Action
Letters. Note: Approval letters are discussed under section VII.
2. Prepares letters involving Clinical, CMC, and establishment issues that will require review
and/or concurrence from the appropriate individuals in the product office and the DMPQ
division director and branch chief.
a. IR and CR letters will be issued over the signature of the Office Director (or
designate) of the Office that is administratively processing the BLA.
b. DR letters will be signed according to Office specific procedures.
3. Draft letters should be circulated electronically for a 72 hour comment period to allow
review by all committee members and their supervisors.
4. CBER generated letters that have been electronically signed by the appropriate personnel
and imported into the EDR do not have to be printed and sent to DCC for archiving.
5. Ensures the appropriate data is entered into RMS-BLA.
VI. BLA: Pre-Approval and Pre-Licensure Inspectional Activities
A. Review Committee: Inspectional Activities
1. Questions to be addressed during the inspection should be forwarded to the inspection
team two weeks prior to the inspection
2. Members of the review committee that participate in the inspection (product specialists)
are required to write their portions of the inspection report and forward to DMPQ,
generally within 30 days after the inspection.
B. DMPQ Team Member: Inspectional Activities
1. Takes the lead responsibility for the inspection except as specified in section VI.C. The
inspection team may include both product and DMPQ reviewers from the review
committee.
2. Confirms that all inspection team members have in-date credentials. (See SOPP 8505:
Nomination and Approval of CBER Inspectors and Product Specialists Assigned to
Conduct Inspections of Biological Products).
3. Notifies the Division of Inspections and Surveillance (DIS), OCBQ, and the Review
Committee, when the inspection is scheduled or prepares an inspection waiver memo.
4. Notifies Office of Regulatory Affairs (ORA) contact according to the appropriate
compliance program guide
5. Ensures the Establishment Inspection Report (EIR) is written and the firm's responses to
FDA Form 483 are evaluated
6. Sends inspection close-out memo and supporting documents to OCBQ/DIS.
7. Upon completion of the inspection and resolution of any inspection issues, prepares the
inspection tab for the final action package per DCC Procedure Guide 11: Procedure for
Filing Pre-license/Pre-approval Inspection Material. The tab will include the EIR,
exhibits, response(s), and the EIR close-out memorandum.
8. A copy of the EIR should be forwarded to DIS/OCBQ.
C. Blood and Plasma Branch, DBA, OBRR: Inspectional Activities
7 of 12 8/8/2008 11:22 AM

8. FDA/CBER - SOPP 8401: Administrative Processing of Biologics Licen... http://www.fda.gov/cber/regsopp/8401.htm
1. Takes the lead responsibility for the pre-licensure inspection for blood establishments
including coordinating and leading the inspection.
2. Confirms that all inspection team members have in-date credentials.
3. Notifies DIS/OCBQ when the inspection is scheduled.
4. Coordinates and leads the inspection
5. Writes the EIR and reviews the firm's Form 483 responses
6. Sends inspection close-out memo and supporting documents to DIS/OCBQ
7. Upon completion of the inspection and resolution of any inspection issues, prepares the
inspection tab for the final action package per DCC Procedure Guide 11: Procedure for
Filing Pre-license/ Pre-approval Inspection Material. The tab will include the
Establishment Inspection Report (EIR), exhibits, response(s), and the inspection close-out
memorandum and the endorsement.
D. Division of Inspections and Surveillance (DIS): Inspectional Activities
1. Prepares and sends a reviewed and redacted (as necessary) copy of the EIR to the firm
consistent with the approach described in ORA's FMD – 145.
2. The inspection tab of the final action package is forwarded to the RPM per DCC
Procedure Guide 11: Procedure for Filing Pre-license/Pre-approval Inspection Material.
3. For blood and blood components only
a. Notifies ORA of scheduled inspections and invites them to participate in the
CBER-led inspection.
b. Prepares Endorsement based on the inspection documentation and the inspection
close-out memo provided by BPB/DBA.
c. Returns inspection materials to BPB reviewer with the endorsement.
E. RPM: Inspectional Activities
1. If necessary, confirms with the DMPQ reviewer that pre-approval inspection teams have
been identified and the inspection(s) initiated, in accordance with SOPP 8410:
Determining When Pre-License/Pre- Approval Inspections are Necessary
2. Ensures completion of the inspection information in RMS-BLA and inclusion in the
complete BLA final action package
VII. BLA: Final Action Activities
A. Review Committee: Approval Activities
1. Ensures that all appropriate documentation (review memos, telecons, etc ) is entered in
RMS-BLA and either imported into the EDR or forwarded to the RPM for inclusion in the
final action package prior to routing the file for approval. All review memos should be
signed by the reviewer and have the concurrence of the supervisor(s) before entry or
routing.
B. Product Review Branch (PRB): Approval Activities
1. Ensures that all lots submitted in support of an application have been processed and any
necessary testing has been satisfactorily completed. Documents this step on the Licensing
Action Recommendation Memorandum (LARM) before approval
2. Obtains signoff from the Director, DMPQ/OCBQ on the Lot Release Testing Plan;
forwards to QAS.
C. Division of Case Management (DCM)/OCBQ: Approval activities
1. Issues the compliance status check upon completion by sending via email or hard copy to
the requestor per SOPP 8407: Compliance Status Checks
D. RPM: Approval Activities
1. Pre-Approval Notification:
Notifies the Office of the Center Director and the Division of Communication and
Consumer Affairs (DCCA), Office of Communication, Training and Manufacturer's
Assistance (OCTMA) by including this information in OCTMA's weekly CBER summary
report approximately four weeks prior to approval for a new indication or one for which
there is significant public interest of the expected approval
2. Ensures that the compliance status check is acceptable. Notifies the committee chair if the
compliance status check is unacceptable.
8 of 12 8/8/2008 11:22 AM

9. FDA/CBER - SOPP 8401: Administrative Processing of Biologics Licen... http://www.fda.gov/cber/regsopp/8401.htm
3. Ensures the compliance check request and response are entered into RMS-BLA and
included in the final action package.
4. Verifies with PRB that lots are available for release at the time of approval and that the
appropriate review and sign-off on the lot release protocols have been completed.
5. Ensures that the CBER Lot Release Testing Plan and Protocol Review Worksheet have
been reviewed and signed off.
6. Prepares the Licensing Action Recommendation Memorandum (LARM).
a. The signoff routing for the LARM should include individuals listed on the form
7. Prepares the Approval Letter in accordance with SOPP 8405: Complete Review and
Issuance of Action Letters.
a. Will bear the signature of the product Office Director and the OCBQ Office
Director,
1. If the applicant already has a license number, the approval letter will be signed
by the product Office Director only. However, the letter will be routed through
the Division Director, DMPQ
2. Approval letters for blood and blood components are signed by the OBRR
Office Director or designate only
b. The draft approval letter should be circulated electronically for a comment period 72
hours prior to final routing.
8. Ensures that pertinent secure emails are reflected in RMS-BLA and incorporated as part of
the administrative record.
9. Ensures that a quality control check of the final action record file has been performed and
all information is documented and entered into RMS-BLA before the 60 day RMS-BLA
lockdown on data entry.
a. Once the RMS-BLA lockdown occurs, any documentation that needs to be added or
deleted will need the authorization of the Associate Director for Review
Management. The authorization request will go through the appropriate Division and
Office Director.
10. Ensures that the status of the application is changed in RMS-BLA no later than 2 working
days after approval
11. Sends the completed final action package to DCC for filing. Refer to DCC Procedure
Guide 8: Procedure for Filing Final Action Packages Containing FDA Correspondence
for Marketable Applications or DCC Procedure Guide 9: Procedure for Filing Multiple
Product Final Action Packages Containing FDA Correspondence for Marketable
Applications.
a. If applicable, the Summary of Basis for Approval (SBA) or cover memorandum
from the SBA Equivalent reviews, and FONSI will be filed in the final action
package behind the LARM
12. Ensures that the applicant is notified of the product approval (by telephone or facsimile)
and the hard copy of the letter is sent
13. Ensures that copies of the dated approval letter or electronic notification are distributed to:
a. the Director of the appropriate product Office,
b. the Director of the Applications Division/Regulatory Management Staff,
c. members of the review committee and their respective Division Directors,
d. RIMS (HFM -110),
e. PRB (HFM – 672) so that lots may be released
f. DCCA/OCTMA ( (HFM-43) include patient package insert if applicable)
g. Communication Technology Branch (CTB)/DCCA/OCTMA for web posting per
SOPP 8105: Submitting Documents for the CBER Web Sites.
h. APLB/DCM/OCBQ (HFM-602) (include patient package insert if applicable)
i. Director, Division of Epidemiology (DE)/OBE (HFM-220) (include patient package
insert if applicable)
j. QAS (HFM-4)
14. Ensures that when approving a new or expanded clinical indication a copy of the final draft
9 of 12 8/8/2008 11:22 AM

10. FDA/CBER - SOPP 8401: Administrative Processing of Biologics Licen... http://www.fda.gov/cber/regsopp/8401.htm
labeling, or final labeling if available, is sent to the Office of the Center Director and that a
copy of the SBA (or Equivalent) is sent to DCCA/OCTMA per SOPP 8106: Submission of
Product Approval Information for Dissemination to the Public
E. RPM: Withdrawal activities
1. Prepares the withdrawal acknowledgement letter to be sent to the applicant in accordance
with SOPP 8405: Complete Review and Issuance of Action Letters.
a. The application withdrawal acknowledgement letter will bear the signature of the
product Office Director or designate.
2. Ensures that a quality control check has been performed on all information documented
and entered into RMS-BLA before the 60 day RMS-BLA lockdown on data entry.
a. Once the RMS-BLA lockdown occurs, any documentation that needs to be added or
deleted will need the authorization of the Associate Director for Review
Management. The authorization request will go through the appropriate Division and
Office Director.
3. Ensures that the status of the application is changed in RMS-BLA no later than 2 working
days after withdrawal
4. Sends the application, all appropriate CBER generated correspondence, and a copy of the
signed withdrawal acknowledgement letter to DCC for filing. See DCC Procedure Guide
8: Procedure for Filing Final Action Packages Containing FDA Correspondence for
Marketable Applications or DCC Procedure Guide 9: Procedure for Filing Multiple
Product Final Action Packages Containing FDA Correspondence for Marketable
Applications, as appropriate.
a. CBER generated documents that are signed electronically and imported into the
EDR do not need to be printed and sent to DCC for filing.
5. Ensures the withdrawal acknowledgement letter is distributed to the product applications
Division Director, the DMPQ Division Director, and QAS.
6. Effective Date
March 12, 2007
7. References
Guidance for Industry Information Request and Discipline Review Letters Under the Prescription Drug User
Fee Act
Guidance for Industry Providing Regulatory Submissions in Electronic Format – Biologics Marketing
Applications (BLA, PLA/ELA, and NDA) November 1999 revised
SOPP 8001.4 Review of CBER Regulated Product Proprietary Names
SOPP 8101.1 Scheduling and Conduct of Regulatory Review Meetings with Sponsors and Applicants
SOPP 8104: Documentation of Telephone Contacts with Regulated Industry
SOPP 8105: Submitting Documents for the CBER Web Sites (CBER's Intranet)
SOPP 8106 Submission of Product Approval Information for Dissemination to the Public
SOPP 8114: Administrative Processing of Documents Received Prior to Submitting Investigational or
Marketing Applications (Pre-Application)
SOPP 8401.1 Issuance and Review of Responses to Information Requests and Discipline Review Letters to
Pending Applications
SOPP 8401.3 Filing Action: Communication Options
10 of 12 8/8/2008 11:22 AM

11. FDA/CBER - SOPP 8401: Administrative Processing of Biologics Licen... http://www.fda.gov/cber/regsopp/8401.htm
SOPP 8401.4 Review Responsibilities for the CMC Section of Biologic License Applications and
Supplements
SOPP 8401.5 Processing of Animal Component Information Submitted in Investigational and Marketing
Applications/Notifications
SOPP 8404 Refusal to File Procedure for Biologics License Applications
SOPP 8405: Complete Review and Issuance of Action Letters
SOPP 8406: Verification of User Fee Data Sheet and Payment
SOPP 8407 Compliance Status Checks
SOPP 8408: Collaboration of CBER Offices on Issues Related to the Release of Pre-Licensing and Routine
Lots
SOPP 8410 Determining When Pre-License/Pre-Approval Inspections are Necessary
SOPP 8412 Review of Product Labeling
SOPP 8505 Nomination and Approval of CBER Inspectors and Product Specialist Assigned to Conduct
Inspections of Biological Products
Note: DCC Procedure Guides are located on CBER's Intranet
DCC Procedure Guide 8: Procedure for Filing Final Action Packages Containing FDA Correspondence for
Marketable Applications
DCC Procedure Guide 9: Procedure for Filing Multiple Product Final Action Packages Containing FDA
Correspondence for Marketable Applications
DCC Procedure Guide 11: Procedure for Filing Pre-License/Pre-Approval Inspection Material
DCC Procedure Guide 22: Procedure for Processing, Routing, and Storing Electronic Submissions
8. History
Version
Written/Revised Approved Approval Date Number Comment
Linda Dixon Robert A. Yetter, April 30, 2007 6 Revised to include
PhD information on PTS.
RMCC Robert A. Yetter, March 9, 2007 5 Incorporates changes to
PhD describe lot release activities
associated with product
review and to include
additional review activities
RMCC Robert A. Yetter, May 11, 2003 4 Changes incorporating new
PhD SOPP 8104.3: Filing Action:
Communications Options
RMCC Robert A. Yetter, October 2, 2002 3 Changes accommodating
PhD PDUFA III and other updates
11 of 12 8/8/2008 11:22 AM

12. FDA/CBER - SOPP 8401: Administrative Processing of Biologics Licen... http://www.fda.gov/cber/regsopp/8401.htm
RMCC Robert A. Yetter, February 22, 2000 2 Incorporates changes
PhD necessitated by publication
of BLA final rule (64 FR
56441) and Biostatistics &
Epidemiology change from
Division to Office
September 10, 1997 1 Original
Updated: May 1, 2007
12 of 12 8/8/2008 11:22 AM